2023, Volume 26, Issue 7
Engineering >> 2023, Volume 26, Issue 7 doi: 10.1016/j.eng.2023.01.006
Serum IgG Glycan Hallmarks of Systemic Lupus Erythematosus
a State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
b Guangdong–Hong Kong–Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou 510000, China
c Peng Cheng Laboratory, Shenzhen 518055, China
d National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
e State Key Laboratory of Quality Research in Chinese Medicine & Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 999078, China
f Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
g Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
h The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
i Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai 519020, China
# These authors contributed equally to this work.
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Abstract
Systemic lupus erythematosus (SLE) is a debilitating autoimmune disorder characterized by unknown pathogenesis and heterogeneous clinical manifestations. The current existing serum biomarkers for SLE have limited sensitivity or specificity, making early and precise diagnosis difficult. Here, we identified two N-glycans on serum immunoglobulin G (IgG) as excellent diagnostic biomarkers for SLE based on indepth glycomic analyses of 389 SLE patients and 304 healthy controls. These two N-glycan biomarkers are specific for diagnosing SLE, as no significant changes in these biomarkers were observed in other systemic autoimmune diseases that are easily confused with SLE, such as rheumatoid arthritis, primary Sjögren's syndrome, or systemic sclerosis. Notably, the two N-glycan biomarkers proved to be autoantibody-independent and all-stage patient suitable. The two N-glycan biomarkers are demonstrated to be located on the Fc region based on fragment-specific glycan analysis and glycopeptide analysis, suggesting their close correlation with disease activity. Enzyme analyses revealed dysregulation of a series of glycotransferases in SLE, which might be responsible for the observed glycan alteration. Our findings provide insights into efficient population screening based on serum IgG glycosylation and potential new pathogenic factors of SLE.
Keywords
Systemic lupus erythematosus ; N-glycans ; Diagnostic indicators
SupplementaryMaterials
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